The Effect of Safflower Yellow Pigment on Myocardial Remodeling after Myocardial Infarction in Rats
Objective To observe the impact of safflower yellow pigment(SY)on myocardial remodeling after acute myocardial infarction(AMI),and explore its relationship with adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)signaling pathway.Methods AMI rat models were constructed by ligating the left anterior branch of coronary artery.They were randomly divided into Model group,losartan group(10 mg/kg),SY low-dose group(8 mg/kg),SY high-dose group(32 mg/kg),and SY + Compound C group(32 mg/kg SY+10 mg/kg Compound C),and sham operation(Sham)group were set up,with 12 rats in each group.After 4 weeks of continuous treatment,the indexes of cardiac function were measured by echocardiography;HE and Masson staining were used to observe the changes of myocardial tissue,calculate the collagen volume integral(CVF),and measure the diameter of myocardial cells in rats;the levels of lactate dehydrogenase(LDH)and superoxide dismutase(SOD)in myocardium were measured by enzyme-linked immunosorbent assay(ELISA);the expression levels of collagen Ⅰ,Ⅲ(COL-I,COL-Ⅲ),B-type natriuretic peptide(BNP),atrial natriuretic peptide(ANP),microtubule associated protein 1 light chain 3 Ⅱ/LC3-Ⅰ(LC3-Ⅱ/LC3-Ⅰ),AMPK,autophagy associated protein P62,Beclin-1,phosphorylated AMPK(p-AMPK),mTOR,phosphorylated mTOR(p-mTOR)proteins were detected by Werstern blot.Results Compared with Sham group,myocardial cells in Model group were hypertrophy and myocardial fibers were disordered,LVFS,LVEF,the expression levels of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,p-AMPK,p-mTOR proteins,and the level of SOD decreased(P<0.05),LVEDD,LVESD,myocardial cell diameter,the expression levels of CVF,COL-Ⅰ,COL-Ⅲ,BNP,ANP and P62 proteins,and the level of LDH increased(P<0.05);compared with the Model group,the myocardial cells of the losartan group and SY low and high dose groups were smaller,and the arrangement of myocardial fibers tended to be normal,LVFS,LVEF,the expression levels of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,p-AMPK,p-mTOR proteins,and the level of SOD increased(P<0.05),LVEDD,LVESD,myocardial cell diameter,the expression levels of CVF,COL-Ⅰ,COL-Ⅲ,BNP,ANP and P62 proteins,and the level of LDH decreased(P<0.05);compared with SY high dose groups,the myocardial cells of rats in SY+Compound C group were hypertrophic and the myocardial fibers were disordered,LVFS,LVEF,the expression levels of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,p-AMPK,p-mTOR proteins,and the level of SOD decreased(P<0.05),LVEDD,LVESD,myocardial cell diameter,the expression levels of CVF,COL-Ⅰ,COL-Ⅲ,BNP,ANP and P62 proteins,and the level of LDH increased(P<0.05).Conclusion SY can improve the antioxidant capacity of AMI myocardium,reduce the degree of myocardial hypertrophy,alleviate the process of myocardial fibrosis,and reverse myocardial remodeling,which may be related to the activation of AMPK/mTOR signal pathway and the up regulation of myocardial autophagy.
Ventricular remodelingSafflower yellow pigmentMyocardial infarctionAdenosine monophosphate-activated protein kinaseSirolimus target protein